Real-time imaging and spectroscopy during microwave assisted chemistry

ABSTRACT

An instrument and associated method are disclosed for conducting microwave assisted chemical reactions. The instrument includes a microwave cavity, preferably a closed microwave cavity, for conducting microwave assisted chemical reactions, and a source for applying microwave radiation within the cavity and to a vessel and its contents. The instrument also includes an illumination source for illuminating the vessel and its contents, as well as means for visually observing the vessel and its contents, an infrared detector for monitoring the temperature of the vessel and its contents, and means for preventing the illumination source from saturating the infrared detector, thereby enabling concurrent visual observation and infrared monitoring.

RELATED APPLICATIONS

This is a divisional application of Ser. No. 11/209,970 filed Aug. 23,2005 and now U.S. Pat. No. ______.

BACKGROUND

The present invention relates generally to the field ofmicrowave-assisted chemistry techniques, and in particular relates totechniques of monitoring microwave-assisted chemical reactions.

Microwave-assisted chemistry techniques are generally well establishedin the academic and commercial arenas. Microwaves have some significantadvantages in heating (or otherwise supplying energy to) certainsubstances. In particular, when microwaves interact with substances withwhich they can couple, most typically polar molecules or ionic species,the microwaves can immediately create a large amount of kinetic energyin such species, which can provide sufficient energy to initiate oraccelerate various chemical reactions. Microwaves also have an advantageover conduction heating in that the surroundings do not need to beheated because the microwaves can react instantaneously with the desiredspecies.

The term “microwaves” refers to that portion of the electromagneticspectrum between about 300 and 300,000 megahertz (MHz) with wavelengthsof between about one millimeter (1 mm) and one meter (1 m). These are,of course, arbitrary boundaries, but help quantify microwaves as fallingbelow the frequencies of infrared (IR) radiation and above thosereferred to as radio frequencies. Similarly, given the well-establishedinverse relationship between frequency and wavelength, microwaves havelonger wavelengths than infrared radiation, but shorter than radiofrequency wavelengths.

Because of their wavelength and energy, microwaves have beenhistorically most useful in driving robust reactions or reactions inrelatively large sample amounts, or both. Stated differently, thewavelengths of most microwaves tend to create multi-mode situations incavities in which the microwaves are being applied. In a number of typesof chemical reactions, this offers little or no disadvantage, andmicrowave techniques are commercially well established for reactionssuch as digestion or loss-on-drying moisture content analysis.

Relatively robust, multi-mode microwave techniques, however, tend to beless successful when applied to small samples of materials. Althoughsome chemistry techniques have the obvious goal of scaling up a chemicalreaction, in many laboratory and research techniques, it is oftennecessary or advantageous to carry out chemical reactions on smallsamples. For example, the availability of some compounds may be limitedto small samples. In other cases, the cost of reactants may discouragelarge sample sizes. Other techniques, such as combinatorial chemistry,use large numbers of small samples to rapidly gather a significantamount of information, and then tailor the results to provide thedesired answers, such as preferred candidates for pharmaceuticalcompounds or their useful precursors.

Microwave devices with larger, multimode cavities that are suitable forother types of microwave-assisted techniques (e.g., drying, digestion,etc.) are generally less-suitable for smaller organic samples becausethe power density pattern in the cavity is relatively non-uniform.

Accordingly, the need for more focused approaches to microwave-assistedchemistry has led to improvements in devices for this purpose. Forexample, in the commercially available devices sold under the assignee's(CEM Corporation, 3100 Smith Farm Road, Matthews, N.C. 28106) DISCOVER®,EXPLORER®, VOYAGER®, NAVIGATOR™, LIBERTY™, and INVESTIGATOR™ trademarkshave provided single mode focused microwave devices that are suitablefor small samples and for sophisticated reactions such as chemicalsynthesis.

The very success of such single mode devices has, however, createdassociated problems. In particular, the improvement in power densityprovided by single-mode devices can cause significant heating in smallsamples, including undesired over-heating in some circumstances. Theability to monitor the temperature of a microwave assisted chemicalreaction aids in avoiding these difficulties.

One technique for monitoring a temperature change is through the use ofinfrared (IR) temperature monitoring. An IR detector monitors infraredradiation emitted by the vessel or its contents and can do so withoutdirectly contacting the vessel. Accordingly, the detector can be locatedin a position, either inside or near the cavity, that avoidsinterference with microwaves. Infrared temperature monitoring can alsoproduce a measurement that is more representative of the entire sample,whereas traditional thermometers and temperature probes can tend toproduce temperature measurements for primarily localized areas.

Moreover, because infrared radiation, as previously discussed, hasdifferent wavelengths than microwaves, the detector can accuratelymeasure the temperature of the emitted infrared radiation withoutinterfering with the microwave heating process, or vice versa.Temperature probes and traditional thermometers may be affected bymicrowave heating, resulting in the addition of extra heat to the sampleor an inaccurate temperature reading.

As is known to those having ordinary skill in the art, organic reactionsare often monitored visually to detect, for example, a color change orthe presence of a precipitate. These physical changes are oftenindicative of the progress of a reaction, including completion, and canaid in determining the time of reaction (rate). For example, lack of aphysical change could indicate that more time is needed. Conversely, aphysical change occurring earlier than expected could indicate a fasterreaction time. The ability to recognize a delayed or early reactionduring heating enables the chemist to save time, either by stopping areaction or by continuing the reaction, thereby avoiding the necessityof repeating the reaction with a longer reaction time. Other physical orchemical changes that are beneficially observed visually include changesin absorbance, emission, light scattering, and turbidity.

The capability to observe visible changes (or the lack thereof) in anongoing reaction can also provide the opportunity to avoid undesiredside reactions and to evaluate and identify optimum reaction conditions,particularly including optimum temperatures or temperature ranges.

Most single mode microwave instruments, however, require closedcavities, thus making direct visual observation of reactions difficultor impossible. Furthermore, a microwave cavity must internally reflect,rather than transmit, the relevant wavelengths of electromagneticradiation. Thus, cavity walls transparent to visual radiation willgenerally be (unfavorably) transparent to microwave radiation as well. Atransparent cavity will not, of course, contain microwave radiation,regardless of mode.

As an independent problem, and even if cavity walls or wall portionsoffer some visibility (as in the screened doors of many domestic kitchenmicrowave ovens), the light sources providing the illumination, such asincandescent, fluorescent, and other common visual sources, ofteninclude an infrared component. The presence of the infrared componentcan—and typically will—interfere with or saturate an infraredtemperature detector, thereby compromising or defeating its performance.

SUMMARY

In another aspect, the invention is a method of carrying out microwaveassisted chemical reactions including applying microwave radiationwithin a cavity and to a reaction vessel in the cavity and reactants inthe reaction vessel. The method further includes concurrently monitoringinfrared radiation emitted from the reaction vessel and reactants todetermine the temperature of the vessel contents, while concurrentlyilluminating and visually monitoring the reactants with wavelengthsother than infrared wavelengths.

In yet another aspect, the invention is an apparatus for conductingmicrowave assisted chemical reactions. The apparatus includes amicrowave-transparent vessel in a microwave cavity, a source forapplying microwave radiation within the cavity and to the vessel and itscontents, and an illumination source for illuminating the vessel and itscontents. The apparatus also includes means for visually observing thevessel and its contents, an infrared detector for monitoring thetemperature of the vessel or its contents, and means for preventing theillumination source from saturating the infrared detector, therebyenabling concurrent visual observation and infrared monitoring.

In another aspect, the invention is a method of carrying out microwaveassisted chemical reactions including placing reactants in amicrowave-transparent vessel and positioning the vessel and its contentsinside a microwave cavity. The method further includes applying acontinuous single mode of microwave radiation within the cavity and tothe vessel and its contents while concurrently monitoring infraredradiation emitted from the reactants to determine the temperature of thevessel contents and illuminating and visually monitoring the reactantsto determine the progress of a reaction. Additionally, the methodincludes adjusting the microwave power in response to a monitored changein the reactants in the vessel.

In yet another aspect, the invention is a method of carrying outmicrowave assisted chemical reactions including applying a continuoussingle mode of microwave radiation within a cavity and to a reactionvessel in the cavity and reactants in the reaction vessel, andintermittently monitoring infrared radiation emitted from the reactionvessel and the reactants to determine the temperature of the vesselcontents, and illuminating and visually monitoring the reactants.

In a further aspect, the invention is an apparatus for conductingmicrowave assisted chemical reactions in a cavity including a microwavetransparent vessel, a source for applying a continuous single mode ofmicrowave radiation within the cavity and to the vessel and itscontents, and an illumination source for illuminating the vessel and itcontents. The apparatus further includes means for visually observingthe vessel and its contents, an infrared detector for monitoring thetemperature of the vessel or its contents, and means for preventing theillumination source from saturating the infrared detector.

The foregoing and other aspects and embodiments of the invention willbecome clearer based on the following detailed description taken inconjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of the elements of an instrument inaccordance with one embodiment of the invention; and

FIG. 2 is a schematic diagram of certain elements of an instrument inaccordance with another embodiment of the invention.

FIG. 3 is another schematic diagram of selected elements of aninstrument in accordance with another embodiment of the invention.

FIG. 4 is a schematic matrix illustrating the collection of dataaccording to an embodiment of the invention.

DETAILED DESCRIPTION

The present invention is a method and apparatus for conducting microwaveassisted chemical reactions including real-time temperature and visualmonitoring. Real-time temperature and visual monitoring provide bettercontrol of reaction rate and conditions.

FIG. 1 is a schematic diagram of one aspect of the invention. Accordingto this aspect, the invention is an instrument broadly designated at 10for conducting microwave assisted chemical reactions. The instrument 10includes a microwave cavity 12, preferably a closed microwave cavity,for conducting microwave assisted chemical reactions. The instrument 10further includes a source, illustrated as the diode 14 for applyingmicrowave radiation within the cavity 12 and to a vessel 16 and itscontents. The instrument 10 also includes an illumination sourceillustrated by the lamp symbol 20 that emits in the visible wavelengthsfor illuminating the vessel 16 and its contents, as well as means forvisually observing the vessel 16 and its contents. The apparatus alsoincludes an infrared detector 22 for monitoring the temperature of thevessel 16 and its contents, and means illustrated as the filter 21 forpreventing the illumination source 20 from saturating the infrareddetector 22, thereby enabling concurrent visual observation and infraredmonitoring.

FIG. 1 shows the illumination source 20, the filter 21 and a fiber opticline 23 entering the cavity 12 separately from the location of theobservation port 26 and its related fiber optic 27 and its potentialconnection to the lens 28, the camera 32 or the spectrometer 34 in amanner discussed further later herein.

It will be understood, of course, that although FIG. 1 illustrates theseelements separately for purposes of clarity, a single fiber optic linecould be used to carry both the illumination wavelengths from the sourceto the cavity as well as providing visible access for observationpurposes. Accordingly, FIG. 1 is descriptive and exemplary rather thanlimiting of this and other aspects of the invention.

In some embodiments, the instrument 10 can include a waveguide 24 incommunication with the source 14 and the cavity 12 to direct themicrowave radiation in the desired orientation.

In another embodiment, the source 14 propagates a continuous single modeof microwave radiation in the cavity 12. Because of the nature ofmicrowaves, which follow well understood laws of wave propagation, theproduction of a single mode is most often accomplished by designing acavity 12 having a geometry that supports a single mode at a wavelengthproduced by the source 14. For example, in the United States, 2450megahertz (MHz) is one of the regulated frequencies (wavelengths)reserved for laboratory microwave use. As used herein and generallywell-understood in this field, the term “mode” refers to the permitted(i.e., with respect to principles of physics) electromagnetic fieldpattern within a cavity.

Microwave modes are generally referred to by the TE_(n,l,m) designation(TE for the magnetic field) where the subscripts refer to the number ofnulls in the propagated direction. Cavities 12 that can support singlemodes are set forth in the art and are generally understood by thosefamiliar with microwaves and their propagations. An exemplary cavity 12for propagating a single mode of microwave radiation is set forth inU.S. Pat. No. 6,288,379, incorporated herein by reference. The inventionis not, however, limited to single mode techniques or cavities.

Any appropriate microwave source 14 can be used that is consistent withthe other aspects of the invention. Typical sources such as magnetrons,klystrons, or solid state sources, such as a Gunn diodes, can be used inthe present invention. In an exemplary embodiment, the application ofcontinuous microwave radiation is accomplished using a resonant inverterswitching power supply as set forth in previously incorporated U.S. Pat.No. 6,288,379. Thus, the term “continuous” is used herein in adescriptive rather than an absolute sense and refers to applyingradiation from a source while driving the source at a frequency greaterthan about 60 hertz. More preferably, the source is driven at afrequency greater than about 600 hertz, even more preferably at greaterthan about 6000 hertz, and most preferably at frequencies between about10,000 and about 250,000 hertz. As described in the '379 patent, thispermits the power to be applied at a more even level over a longerperiod of time than in conventional devices which operate on 50 cycle(typical in Europe) or 60 cycle alternating current (standard in theUnited States).

Because one of the goals of the invention is to provide visualinformation, in exemplary embodiments, the illumination source 20 is avisual illumination source. Preferred visual illumination sourcesinclude one or more of LEDs, fiber optic lights, fluorescent lights,incandescent lights, broad band light sources, and other visual lightsources known in the art. The term “visual” is used herein in itsordinary sense with respect to illumination, i.e., the visiblefrequencies are those to which the human eye normally responds. Althoughexact boundaries can be arbitrary, visible wavelengths are functionallydescribed as those falling between the infrared and ultraviolet portionsof the electromagnetic spectrum. Described numerically, they fallbetween about 400 and 700 nanometers.

In the illustrated embodiment, the illumination source 20 includes thefiber optic light pipe 23 inserted into the cavity 12.

The means for visually observing the vessel 16 and its contents may beselected from a camera (video or still, and based on film, magneticmedia, or digital media) 32, a spectrophotometer 34, and other visualobserving means known in the art. A monitor 36 may also be used todisplay the output from the camera 32 or spectrophotometer 34. In anexemplary embodiment, a lens 28 is used to provide a preferred view, forexample a wide angle view, of the inside of the cavity.

The invention may further include a processor 38 in signal communicationwith one or more of the camera 32, spectrophotometer 34 and monitor 36.Connectors 19 (processor to source), 27 (processor to spectrometer), 29(processor to pressure transducer), 30 (processor to temperaturemonitor), and 31 (processor to monitor) schematically illustrate theserelationships. The processor 38 is preferably capable of controlling themicrowave source 14 either automatically or manually, in response todata received from one or more of the camera 32, spectrophotometer 34,and monitor 36. In a preferred embodiment, the processor controls themicrowave source 14 in response to a predetermined monitored changedetected by one or more of the camera 32, spectrophotometer 34, andcomputer 36.

The processor 38 can be selected from among widely available and wellunderstood processors such as the Pentium® series from Intel® (SantaClara, Calif.) that are commonly used in personal computers, orfunctionally equivalent processors from other sources such as AMD®(Sunnyvale, Calif.). In some cases, a commercially-available desktop orlaptop computer can be programmed with software to carry out the desiredcontrol functions while in other circumstances, the processor can beused in cooperation with preprogrammed read only memory (ROM) for thesame purpose. In either case, the skilled person can obtain and use therelevant processor without undue experimentation. General discussions ofcontrol circuits and logic and related devices and systems are widelyavailable, with one common source being Dorf, The Electrical EngineeringHandbook, 2d Ed. (1997, CRC Press), at pages 1104-1107, sections43.6-43.7.

In exemplary embodiments, the means for preventing the illuminationsource from saturating the IR temperature detector 22 prevents infraredradiation emitted by the illumination source 20 from reaching the cavity12. In one embodiment, the means for preventing the illumination sourcefrom saturating the IR temperature detector 22 is a filter 21 thatremoves IR radiation emitted by the illumination source 20. Preferredfilters 21 include well-known and commercially available heat glass thatfilters IR radiation (e.g., HOYA™ glass13 HA-30, San Jose, Calif.).

In another aspect, the invention is a method of carrying out microwaveassisted chemical reactions by applying microwave radiation within acavity, to a reaction vessel in the cavity, and reactants in thereaction vessel, while concurrently monitoring infrared radiationemitted from the reaction vessel and reactants to determine thetemperature of the vessel contents and while concurrently illuminatingand visually monitoring the reactants with wavelengths other thaninfrared wavelengths.

Although the term “vessel” is used herein with respect to both theinstrument and method aspects of the invention, it will be understoodthat the invention is not limited to sealed or unsealed vessels of anyparticular size or shape. Additionally, the term vessel can includeother physical arrangements for handling the reactants, includingflow-through systems.

The temperature is preferably monitored using a device or method thatdoes not interfere with the application and effectiveness of themicrowave radiation. Thus, in preferred embodiments, temperaturemonitoring is carried out optically, by using an IR temperature sensor.An IR sensor is particularly useful when the frequencies being appliedto supply energy to the reactants are other than IR, because theinfrared sensor measures radiation emitted by the vessel or its contentsand does not need to be in direct contact with the vessel. Accordingly,it can be positioned in a spot that does not interfere with themicrowave radiation. Exemplary sources of such IR sensors includeLuxtron® (Santa Clara, Calif.), Ircon® (Niles, Ill.), and LandInstruments International (Newtown, Pa.).

In another embodiment, the method includes placing reactants in amicrowave-transparent vessel, potentially, but not necessarily,including placing the reactants in pressure-resistant vessels which canbe sealed prior to the application of microwave radiation. The vesseland its contents are then placed into a microwave cavity and microwaveradiation, preferably a continuous single mode of microwave radiation,is applied within the cavity to the vessel and its contents whileconcurrently externally cooling the vessel.

The method may also include the step of using various robotic transfersto both place the reactants in a microwave transparent vessel and toplace the vessel and contents into a microwave cavity.

In a preferred embodiment, the microwave cavity, preferably a closedmicrowave cavity, is illuminated by a light source that emits at leastin the visible wavelengths of the electromagnetic spectrum. In oneembodiment, the illuminating step further includes filtering the visiblelight source to remove wavelengths emitted in the infrared region of theelectromagnetic spectrum that would otherwise interfere with thetemperature monitoring step. A preferred method for filtering theinfrared wavelengths includes using a heat glass, such as HOYA™glass—HA-30, to remove IR wavelengths.

In a different embodiment, the illuminating step uses a light sourcethat does not emit in the infrared region of the electromagneticspectrum. For example, white-emitting LED lamps emit over a combinationof narrow ranges of visible wavelengths (red, green, and blue) and donot emit in the infrared region of the electromagnetic spectrum. Suchlamps thereby avoid interfering with the IR temperature detector ormeasurement.

In one exemplary embodiment, illumination of the microwave cavity may beeffected by inserting a fiber optic light pipe into a closed microwavecavity. It may be preferred to use a lens to provide a wider angle viewof the inside of the cavity. The lens may be preferably placed on thecavity end of the illumination light source, for example the fiber opticpipe, to enhance a viewing angle.

In another embodiment, the invention further includes visually recordingthe reaction (e.g., video or still recording, and based on film,magnetic media, or digital media).

The invention provides the capability to moderate the microwaveradiation in response to an observed change, either automatically ormanually. The microwave radiation may be moderated in response to amonitored temperature change, a visually monitored change, or both.Additionally, it may be preferable to moderate the microwave radiation,either automatically or manually, in response to a predeterminedmonitored change.

In a manner consistent with other microwave devices and techniques, theinstrument 10 can also include a pressure transducer 42 which is inpressure communication with the vessel 16 either directly or indirectlyas schematically indicated by the line 43 in FIG. 1. In turn, thetransducer 42 is in signal communication with the processor 38. Inaddition to providing information about the pressure in the vessel, thepressure measurement can be used in a control circuit to moderate theapplication of microwaves in a manner similar to that already describedfor temperature data and for visual observation data.

In yet another embodiment, the method may include directing the visuallymonitored output to a spectrophotometer. The spectrophotometerpreferably monitors chemical changes in the reactants, such asabsorbance, emission, turbidity, and precipitation, as well as otherchemical changes recognizable by those having ordinary skill in the art.

In a preferred aspect, the invention is a method of carrying outmicrowave assisted chemical reactions. The method includes placingcompositions-frequently reactants—in a microwave-transparent vessel,positioning the vessel and its contents inside a microwave cavity, andapplying a continuous single mode of microwave radiation within thecavity and to the vessel and its contents. The method further includesconcurrently monitoring infrared radiation emitted from the reactants todetermine the temperature of the vessel contents while illuminating andvisually monitoring the reactants to determine the progress of areaction, as well as adjusting the microwave power in response to amonitored change in the reactants in the vessel.

It will be understood, of course, that although the term “reactants” isused frequently herein, the method is not limited to starting materials,but can be applied to any appropriate compositions.

In one embodiment, the microwave power may be adjusted either manuallyor automatically in response to the monitored change in the reactants inthe vessel. Moreover, the microwave power may be adjusted in response toa change monitored by the temperature sensor or in response to a changemonitored visually. Examples of visually monitored changes includechanges in absorbance, emission, light scattering, turbidity, solidscontent, and other visual reaction changes recognized by those havingordinary skill in the art. In one embodiment, the microwave power may beadjusted, either manually or automatically, in response to apredetermined monitored change (e.g., when the reaction reaches apredetermined temperature or when a color change occurs).

In a further embodiment, the step of visually monitoring the reactionincludes illuminating the reaction vessel and the reactants in thereaction vessel with a visual light source. The illuminating stepfurther includes limiting the monitored IR wavelengths to IR wavelengthsproduced by the reaction with, for example, a filter or an LED asdiscussed above.

FIG. 2 is another schematic diagram illustrating relevant portions of analternative embodiment of the invention in which a modulator isincorporated to prevent infrared radiation from the illumination source20 from interfering with the infrared temperature measurement. In FIG.2, like elements carry like reference numerals. It will be understoodthat for the sake of clarity FIG. 2 is limited to portions of theinstrument and that the instrument can also include any or all of theelements described with respect to FIG. 1.

Accordingly, FIG. 2 illustrates the cavity 12 and the vessel 16, alongwith the infrared temperature detector 22, and the illumination lamp 20.In order to prevent infrared wavelengths produced by the lamp 20 frominterfering with the measurements of the infrared detector 22, in thisembodiment the instrument includes the modulator 44 that is in opticalcommunication with the cavity 12 through a single fiber optic connection45. The modulator 44 is also in separate optical communication with theinfrared detector 22 through the fiber optic 46 and with the lamp 20through the fiber optic 47. The modulator 44 periodically (i.e.,time-based) either directs radiation from the lamp 20 to the cavity, orradiation from the vessel to the infrared detector, but never both atthe same time. Accordingly, an instrument incorporating the modulator 44does not require an IR-blocking filter to eliminate interference betweenIR wavelengths generated by the vessel (and its contents) and thoseprovided by the illumination source.

Because the visual frequencies are substantially unaffected by theinfrared frequencies, the camera 32 (or other detector) and its relatedfiber optic 27 need not be included in the modulation system.

The use of the modulator 44 as the means for preventing the illuminationsource 20 from saturating the infrared detector 22 may result inintermittent periods of illumination and non-illumination in the cavity12. During periods of non-illumination, the IR temperature detector 22detects IR radiation emitted from the vessel 16 and its contents 18without interference from IR radiation emitted by the illuminationsource 20.

In another aspect, the invention is a method of carrying out microwaveassisted chemical reactions including applying a continuous single modeof microwave radiation within a cavity, preferably a closed cavity, andto a reaction vessel in the cavity and reactants in the reaction vessel.The method further includes intermittently monitoring infrared radiationemitted from the reaction vessel and the reactants to determine thetemperature of the vessel contents; and intermittently illuminating andvisually monitoring the reactants.

The method may also include placing the reactants in a vessel,preferably a pressure-resistant vessel, and sealing the vessel prior tothe step of applying the microwave radiation. The step of applyingmicrowave radiation preferably includes applying a continuous singlemode of microwave radiation as previously discussed.

In preferred embodiments, the step of intermittently illuminating andvisually monitoring the reactants comprises modulating a light sourcecontaining an IR component to allow intermittent visual observation andinfrared temperature monitoring. The light source may be modulated bytechniques known in the art including, but not limited to, shutters,filter wheels, switches, and combinations thereof.

In one embodiment, the step of illuminating the cavity includesinserting a fiber optic light pipe into a closed cavity. In an exemplaryembodiment, a lens is used to provide a preferred view, for example awide angle view, of the inside of the cavity.

The method preferably further includes visually recording the reaction,as previously discussed, with a camera. The method may also includemoderating the microwave radiation in response to an observed change anddirecting the monitored output to a spectrophotometer to observechemical changes within the reactants.

In describing the invention, it will be understood that a number oftechniques are disclosed. Each of these has individual benefit, and eachcan also be used in conjunction with one or more, or in some cases all,of the other disclosed techniques. Accordingly, for the sake of clarity,this description refrains from repeating every possible combination ofthe individual steps in an unnecessary fashion. Nevertheless, thespecification and claims should be read with the understanding that suchcombinations are entirely within the scope of the invention and theclaims.

In another aspect, the invention comprises converting the image of thevessel and its contents into machine readable format, most typicallydigital format, and forwarding the formatted information to a processor.The processor is preprogrammed (hardware or software based) to control areaction based upon the image The control function can be done based onthe image input standing alone, or in conjunction with other types ofinput. In microwave assisted chemistry, the most typical additionalmeasurable variables include the microwave power, the measuredtemperature of the reaction or the vessel (or both) and the measuredpressure generated by a reaction in a vessel. The use of temperature orpressure or both to control reactions by moderating the application ofmicrowave power through a control circuit has been discussed elsewhere;e.g., commonly assigned U.S. Pat. Nos. 6,866,408; 6,084,226; 5,840,583;and 5,796,080. In the present invention, the image information, whenforwarded to the processor, is used in conjunction with the appliedmicrowave power to make a change in their reaction, or with thetemperature, or with the pressure, or with any two, or with all three ofthese variables.

For example, a color change standing alone can indicate a phase changeor completion of a chemical reaction or sequence of chemical reactions.Accordingly, such color information when converted and forwarded to theprocessor, can be used to control (including starting, stopping,increasing, or decreasing) the microwave power.

The invention is not limited to just such a single point of analysis. Toexpand the example, the processor can be programmed to recognize a colorchange in combination with a set point temperature before making achange or a color change in combination with a set point pressure beforemaking a change, or a color change in combination with both a specificset point temperature and a set point pressure before making a change.

In the same manner, the image, including a change in the image, can beused to signal completion of a reaction even if the reaction does notreach an expected set point temperature or set point pressure. Forexample, in the absence of the image information, controlling theendpoint of a desired reaction scheme would necessarily be based upon aparticular set point temperature or set point pressure.

Using the invention, however, the image information provides evidencethat the reaction was successfully completed before a normal set pointpressure or temperature has been reached. In such cases, the imageinformation provides the capability to recognize the completion of thereaction earlier than with either temperature or pressure measurements.

The invention further comprises compiling matching sets of data on atime basis throughout the desired course of a chemical reaction. In thisaspect, digital images taken at specified times (once per minute, onceper second, multiple times per second) can be precisely matched with theapplied power, the measured temperature, and the measured pressure atthe same specified times. Compiling such information is straightforwardusing processors of conventional capabilities and provides the workingchemist with the ability to replay the progress of the entire reaction(or portions of the reaction as the chemist sees fit) on demand andrepeatedly while also having the capability to compare the measureditems to one another and to the image information on a time selectedbasis.

In another aspect, a mechanical object such as a magnetic stirring bar,can be added to a reaction vessel. In this aspect, the image informationfrom the object provides secondary information about process parametersthat may lack visual indicators. For example, a change in fluidviscosity may not otherwise change the image of the reactants orproducts. The change in behavior of the stirrer bar can, however,provide relevant information about viscosity. Thus, if the stirrer barunder a fixed magnetic field rotates at a known frequency at arecognized viscosity (for example of water) and then is observed duringthe reaction to rotate at a different frequency, the change in rotationfrequency can be observed, digitized, and used to evaluate and predictor determine the viscosity or change in viscosity in the reactionvessel. Other examples will be recognized easily by those of ordinaryskill in this art.

In a related aspect, the invention is a method of microwave assistedchemistry comprising applying microwave radiation to a reaction vesseland its contents, periodically measuring a variable selected from thegroup consisting of the temperature of the vessel and its contents andthe pressure within the reaction vessel, periodically obtaining an imageof the vessel and its contents, converting the obtained images todigital output, and moderating the application of microwaves to thevessel and its contents based on the digital image output and at leastone of the periodic measurements of temperature and pressure.

In this aspect, the moderation of the application of microwaves can alsobe based upon the digital image output and both of the periodicmeasurements of temperature and pressure.

In preferred embodiments, the method comprises obtaining an image of thevessel and its contents in the visual wavelengths because, as notedearlier, these are different from the wavelengths of the appliedmicrowaves and from the infrared wavelengths which are used with certaintypes of optical temperature detectors.

In this aspect, it will be understood that although a visual output canbe produced for a user, the method comprises moderating the applicationof microwaves independently of, and potentially without, a visualdisplay of the obtained images. Stated differently, the method does notrequire an operator to observe the visual image and then moderate theapplication of microwaves. Instead, the images are obtained andconverted to digital output independent of the operator in order tomoderate the application of microwaves.

FIG. 3 is another schematic illustration of some of the instrumentaspects of this embodiment of the invention. Many of the elements ofFIG. 3 are the same as those described with respect to FIGS. 1 and 2,and in such cases they carry the same reference numerals. Similarly, itwill be understood that FIG. 3 is a schematic diagram of certain of theelements of the instrument and is not intended to illustrate all of thepotential variations, but rather to highlight certain features. Forexample, FIG. 3 does not specifically illustrate a cavity, but it willbe understood that microwaves are typically, even if not exclusively,applied to chemical compositions in reaction vessels in cavities.

Thus, FIG. 3 illustrates the microwave source illustrated as the diode14, along with the temperature detector 22 for measuring the temperatureof compositions in the instrument (FIG. 3 illustrates just the vessel16) to which microwaves are applied from the source 14. A pressuretransducer again indicated that 42 measures the pressure generated bycompositions in the vessel 16 to which the microwaves are applied fromthe source 14.

In the embodiment illustrated in FIG. 3, however, the camera 32 (FIGS. 1and 2) is replaced by the image detector 50 which is not necessarily acamera. The detector 50 is capable of obtaining images of compositionsin the instrument while microwaves are being applied from the source 14,and is likewise capable of producing digital output that corresponds tothe obtained images. Detectors that produce digital output based uponvisible light, other wavelengths of light, or other analog input, arewell understood and widely available in the art and can be selected orincorporated by those of skill in this art without undueexperimentation. Accordingly, the detector 50 can have the capability toproduce the digital output directly or, as illustrated in FIG. 3, it canbe used in conjunction with an analog digital converter 51 for producingthe digital output from the obtained images.

In this embodiment, the processor 38 is in signal communication witheither the detector 50 or the converter 51, with the temperaturedetector 22, with the pressure detector 42, and with the microwavessource 14 for moderating the application of microwaves from the source14 to the compositions in the instrument based upon the digital outputfrom the detector (or converter), and in combination with at least oneof the measured pressure and the measured temperature.

In particular, FIG. 3 illustrates that the processor 38 moderates theapplication of microwaves independent of any visual display (e.g., to anoperator) of obtained images. Stated differently, the appearance of thevessel 16 and its contents can be translated directly into digitalinformation for the processor 38 regardless of whether or not it is alsodisplayed on a monitor (e.g. 36 in FIG. 1). Furthermore, because theprocessor 38 can operate independent of any visual display, theinstrument can moderate the application of microwaves without any visualdisplay of obtained images.

In another aspect, the invention is a method of microwave-assistedchemistry comprising obtaining an image of compositions during theapplication of microwave radiation to those compositions at specifictime intervals, combined with measuring the temperature of thecompositions at the same specific time intervals, and combined withmeasuring the pressure generated by the composition at the same specifictime intervals. In this aspect, the microwave power applied to thecompositions is also recorded at the same specific time intervals as theimages and the other information are obtained. A recorded matrix isgenerated from the image, temperature, pressure and power information atthe specific time intervals. Table 1 represents such a matrix.

TABLE 1 Microwave Measured Measured Time Image Power TemperaturePressure T₁ (Image)1 Watts₁ ° C.₁ P₁ T₂ (Image)₂ Watts₂ ° C.₂ P₂ T₃(Image)₃ Watts₃ ° C.₃ P₃ T₄ (Image)₄ Watts₄ ° C.₄ P₄ T₅ (Image)₅ Watts₅° C.₅ P₅ * * * * * * * * * * * * * * * T_(x) (Image)_(x) Watts_(x) C_(x)P_(x)

In many circumstances, the method will comprise obtaining images in thevisible wavelengths, but it will be understood that other wavelengthscould be used as desired or necessary depending upon the image detectorand conversion equipment selected. As in the instrument aspects, therecorded matrix can be generated independent of any visual display ofthe obtained images. If visual images are not required by an operator(for example) for any other purposes, the method can comprise generatingthe recorded matrix without any visual display whatsoever of theobtained images.

FIG. 4 is a schematic diagram of such a matrix. Seven time periods areillustrated and correspond to seven images obtained during themicrowave-assisted chemical reaction. Each of the vessels in FIG. 4 isillustrated with a different pattern in order to schematicallyillustrate the potential appearance changes. It will be understood, ofcourse, that as few as one image change over the course of a givenreaction can be useful in the present invention and that the selectedgroup of seven is taken arbitrarily for illustration purposes.

As illustrated in FIG. 4, each respective time interval-based image canbe associated with a corresponding power level (W), temperature (T) andpressure (P). Using readily available processor power and conventionallyavailable memory, the entire course of the reaction can be stored andthen replayed on demand to obtain a better understanding of theinteraction among and between the power, the temperature, the pressure,and the appearance of the starting materials, products, andintermediates.

In the drawing and specification, there has been set forth preferredembodiments of the invention, and although specific terms have beenemployed, they are used in a generic and descriptive sense only and notfor purposes of limitation, the scope of the invention being defined inthe claims.

1. A method of carrying out microwave assisted chemical reactions, themethod comprising: placing reactants in a microwave-transparent vessel;positioning the vessel and its contents inside a microwave cavity;applying a continuous single mode of microwave radiation within thecavity and to the vessel and its contents; while concurrently monitoringinfrared radiation emitted from the reactants to determine thetemperature of the vessel contents; while concurrently illuminating andvisually monitoring the reactants to determine the progress of areaction; and adjusting the microwave power in response to a monitoredchange in the reactants in the vessel.
 2. A method of carrying outmicrowave assisted chemical reactions according to claim 1 wherein thestep of adjusting the microwave power comprises adjusting the microwavepower in response to a monitored temperature change.
 3. A method ofcarrying out microwave assisted chemical reactions according to claim 1wherein the step of adjusting the microwave power comprises adjustingthe microwave power in response to a visually monitored change.
 4. Amethod of carrying out microwave assisted chemical reactions accordingto claim 1 wherein the step of adjusting the microwave power comprisesadjusting the microwave power in response to a monitored chemical changein the reactants.
 5. A method of carrying out microwave assistedchemical reactions according to claim 1 wherein the step of adjustingthe microwave power in response to a monitored change in the reactantsin the vessel comprises adjusting the microwave power in response to amonitored, predetermined change in the reactants in the vessel.
 6. Amethod of carrying out microwave assisted chemical reactions accordingto claim 1 further comprising visually recording the reaction.
 7. Amethod of carrying out microwave assisted chemical reactions accordingto claim 1 wherein the step of visually monitoring the reactants todetermine the progress of a reaction comprises illuminating the reactionvessel and the reactants in the reaction vessel with a visual lightsource.
 8. A method of carrying out microwave assisted chemicalreactions according to claim 1 wherein the step of illuminating andvisually monitoring the reactants further comprises limiting themonitored IR wavelengths to IR wavelengths produced by the reaction. 9.A method of carrying out microwave assisted chemical reactions, themethod comprising: applying a continuous single mode of microwaveradiation within a cavity and to a reaction vessel in the cavity andreactants in the reaction vessel; intermittently monitoring infraredradiation emitted from the reaction vessel and the reactants todetermine the temperature of the vessel contents; and intermittentlyilluminating and visually monitoring the reactants.
 10. A method ofcarrying out microwave assisted chemical reactions according to claim 9,further comprising placing the reactants in a vessel and sealing thevessel prior to the step of applying the microwave radiation.
 11. Amethod of carrying out microwave assisted chemical reactions accordingto claim 10 wherein the step of placing the reactants in a vesselcomprises placing the reactants in a pressure-resistant vessel.
 12. Amethod of carrying out microwave assisted chemical reactions accordingto claim 9 wherein the step of applying microwave radiation comprisesapplying microwave radiation from a source selected from the groupconsisting of magnetrons, klystrons, and solid state sources.
 13. Amethod of carrying out microwave assisted chemical reactions accordingto claim 9 wherein the step of visually monitoring the reactantscomprises illuminating the reaction vessel and the reactants using alight source that includes the visible wavelengths.
 14. A method ofcarrying out microwave assisted chemical reactions according to claim 9wherein the step of intermittently illuminating and visually monitoringthe reactants comprises modulating a light source containing an IRcomponent to allow intermittent visual observation and infraredtemperature monitoring.
 15. A method of carrying out microwave assistedchemical reactions according to claim 9 wherein the illuminating andvisually monitoring step comprises illuminating the interior of a closedcavity.
 16. A method of carrying out microwave assisted chemicalreactions according to claim 9 wherein the illuminating and visuallymonitoring step comprises inserting a fiber optic light pipe into aspectroscopy port in a closed microwave cavity.
 17. A method of carryingout microwave assisted chemical reactions according to claim 16 furthercomprising monitoring through a lens.
 18. A method of carrying outmicrowave assisted chemical reactions according to claim 17 wherein thestep of monitoring through a lens comprises monitoring through a lens onthe cavity end of the fiber optic light pipe to enhance a viewing angle.19. A method of carrying out microwave assisted chemical reactionsaccording to claim 15 further comprising visually recording thereaction.
 20. A method of carrying out microwave assisted chemicalreactions according to claim 9 further comprising moderating themicrowave radiation in response to an observed reaction change.
 21. Amethod of carrying out microwave assisted chemical reactions accordingto claim 9 wherein the step of visually monitoring the reactants todetermine the progress of a reaction comprises directing the monitoredoutput to a spectrophotometer.
 22. A method of microwave assistedchemistry comprising: applying microwave radiation to a reaction vesseland its contents; periodically obtaining an image of the vessel and itscontents; converting the obtained images to digital output; andmoderating the application of microwaves to the vessel and its contentsbased on the digital image output.
 23. A method according to claim 22further comprising periodically measuring a variable selected from thegroup consisting of the temperature of the vessel and its contents andthe pressure within the reaction vessel and moderating the applicationof microwaves to the vessel and its contents based on the digital imageoutput and at least one of the periodic measurements of temperature andpressure.
 24. A method according to claim 23 comprising moderating theapplication of microwaves to the vessel and its contents based on thedigital image output and both of the periodic measurements oftemperature and pressure.
 25. A method according to claim 22 comprisingobtaining an image of the vessel and its contents in the visualwavelengths.
 26. A method according to claim 22 comprising moderatingthe application of microwaves independently of any visual display of theobtained images.
 27. A method according to claim 22 comprisingmoderating the application of microwaves without any visual display ofthe obtained images.
 28. A method of microwave assisted chemistrycomprising: obtaining an image of compositions during the application ofmicrowave radiation to the compositions at specific time intervals;measuring the temperature of the compositions at the same specific timeintervals as the images are obtained; measuring the pressure generatedby the compositions at the same specific time intervals as the imagesare obtained; recording the microwave power applied to the compositionsat the same specific time intervals as the images are obtained; andgenerating a recorded matrix of the image, temperature, pressure, andpower measurements at the specific time intervals.
 29. A methodaccording to claim 28 comprising obtaining images in the visualwavelengths.
 30. A method according to claim 28 comprising generatingthe recorded matrix independently of any visual display of the obtainedimages.
 31. A method according to claim 28 comprising generating therecorded matrix without any visual display of the obtained images.